Paradoxical recurrent meningitis following therapy of cryptococcal meningitis: an immune reconstitution syndrome after initiation of highly active antiretroviral therapy

Abstract

We report a case of paradoxical recurrent meningitis in response to initiation of highly active antiretroviral therapy in a patient receiving maintenance fluconazole for a previous diagnosis of cryptococcal meningitis. We describe the unusual radiographic and histopathologic findings which are consistent with an immune reconstitution induced paradoxical inflammatory response to residual cryptococcal infection.

CNS–Immune Reconstitution Inflammatory Syndrome in the Setting of HIV Infection, Part 1: Overview and Discussion of Progressive Multifocal Leukoencephalopathy–Immune Reconstitution Inflammatory Syndrome and Cryptococcal–Immune Reconstitution Inflammatory Syndrome

“…The findings of linear perivascular enhancement in the sulci and new meningeal or choroid plexus enhancement have been shown to be imaging indicators of CM-IRIS. 19,90,94 In a case illustrated by Riedel et al, 19 a cerebellar lesion with high FLAIR signal having mass effect on the fourth ventricle was seen to develop in association with an increase in meningeal enhancement 2 weeks after an HIVinfected patient with CM was treated with antiretroviral therapy. While distention of the Virchow-Robin spaces manifested as high T2/FLAIR signal, particularly in the basal ganglia, and gelatinous pseudocysts have been imaging features of cryptococcal meningitis in both the pre-and post-HAART era due to the production of a viscous mucoid material by the acidic polysaccharide capsule of the cryptococcal organism, 95 enhancement of these Virchow-Robin spaces appears characteristic of CM-IRIS as does secondary involvement of the brain parenchyma characterized by areas of high T2/FLAIR signal (Fig 6A), restricted diffusion, and parenchymal enhancement.…”

Immune Restoration Diseases Reflect Diverse Immunopathological Mechanisms

“…Cryptococcal IRD may present either as a paradoxical relapse, secondary to restored immunity to partially treated infections or residual cryptococcal antigens (8,69), or as the unmasking of a subclinical infection present at the time of ART (152). Cryptococcal IRD affects 19 to 50% of patients initiating ART with a prior diagnosis of cryptococcal disease (4,67,81,130).…”

Hipertensão intracraniana na meningoencefalite criptocócica em pacientes soropositivos para o vírus da imunodeficiência humana: estudo de uma série de casos

“…O termo meningoencefalite é mais apropriado que meningite haja vista que na maioria dos casos há envolvimento do parênquima cerebral subjacente às meninges comprovado por estudos histopatológicos (Antinori et al, 2001;King et al, 2002;Breton et al, 2002;Angstwurm et al, 2004).…”

“…A pressão intracraniana pode elevar-se, sendo comumente necessárias repetidas punções liquóricas de alívio ou cirurgia de derivação. Os exames neuroradiológicos que frequentemente não evidenciam alterações características durante o período de meningoencefalite aguda podem apresentar realce de contraste ou criptococomas (Woods et al, 1998;Cinti et al, 2001;King et al, 2002; dessas reações não é clara, mas pode ser devida a um aumento da resposta específica de linfócitos a antígenos microbianos latentes ou inativos e até mortos (Shelbourne & Hamill, 2003). A apresentação clínica destas infecções é freqüentemente atípica, e o diagnóstico difícil, uma vez que as culturas são geralmente negativas.…”

“…A apresentação clínica destas infecções é freqüentemente atípica, e o diagnóstico difícil, uma vez que as culturas são geralmente negativas. O tratamento requer terapia antimicrobiana específica e, ocasionalmente, drogas anti-inflamatórias (Woods et al, 1998;Cinti et al, 2001;King et al, 2002;Breton et al, 2002;Shelbourne & Hamill, 2003;Cattelan et al, 2004).…”